Combinatorial Pharyngeal Taste Coding for Feeding Avoidance in Adult Drosophila.

Taste drives appropriate food preference and intake. In Drosophila, taste neurons are housed in both external and internal organs, but the latter have been relatively underexplored. Here, we report that Poxn mutants with a minimal taste system of pharyngeal neurons can avoid many aversive tastants, including bitter compounds, acid, and salt, suggesting that pharyngeal taste is sufficient for rejecting intake of aversive compounds. Optogenetic activation of selected pharyngeal bitter neurons during feeding events elicits changes in feeding parameters that can suppress intake. Functional dissection experiments indicate that multiple classes of pharyngeal neurons are involved in achieving behavioral avoidance, by virtue of being inhibited or activated by aversive tastants. Tracing second-order pharyngeal circuits reveals two main relay centers for processing pharyngeal taste inputs. Together, our results suggest that the pharynx can control the ingestion of harmful compounds by integrating taste input from different classes of pharyngeal neurons

Blood-based bioenergetic profiling is related to differences in brain morphology in African Americans with Type 2 diabetes.

Blood-based bioenergetic profiling has promising applications as a minimally invasive biomarker of systemic bioenergetic capacity. In the present study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with long-standing Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes. Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology

Energy Landscapes for Proteins: From Single Funnels to Multifunctional Systems

This report advances the hypothesis that multifunctional systems may be associated with multifunnel potential and free energy landscapes, with particular focus on biomolecules. It compares systems that exhibit single, double, and multiple competing structures, and contrasts multifunnel landscapes associated with misfolded amyloidogenic oligomers, which presumably do not arise as an evolutionary target. In this context, intrinsically disordered proteins could be considered intrinsically multifunctional molecules, associated with multifunnel landscapes. Potential energy landscape theory enables biomolecules to be treated in a common framework together with self‐organizing and multifunctional systems based on inorganic materials, atomic and molecular clusters, crystal polymorphs, and soft matter.epsr

Dimensions Underlying Student Ratings of Instruction: A Multidimensional Scaling Analysis

↵MARTHA L. BANZ, Graduate Student, Department of Psychology, University of Oklahoma, Norman, OK 73019.Specializations:Quantitative methods, educational psychology.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The importance of geometry in the corneal micropocket angiogenesis assay

The corneal micropocket angiogenesis assay is an experimental protocol for studying vessel network formation, or neovascularization, in vivo. The assay is attractive due to the ease with which the developing vessel network can be observed in the same animal over time. Measurements from the assay have been used in combination with mathematical modeling to gain insights into the mechanisms of angiogenesis. While previous modeling studies have adopted planar domains to represent the assay, the hemispherical shape of the cornea and asymmetric positioning of the angiogenic source can be seen to affect vascular patterning in experimental images. As such, we aim to better understand: i) how the geometry of the assay influences vessel network formation and ii) how to relate observations from planar domains to those in the hemispherical cornea. To do so, we develop a three-dimensional, off-lattice mathematical model of neovascularization in the cornea, using a spatially resolved representation of the assay for the first time. Relative to the detailed model, we predict that the adoption of planar geometries has a noticeable impact on vascular patterning, leading to increased vessel ‘merging’, or anastomosis, in particular when circular geometries are adopted. Significant differences in the dynamics of diffusible aniogenesis simulators are also predicted between different domains. In terms of comparing predictions across domains, the ‘distance of the vascular front to the limbus’ metric is found to have low sensitivity to domain choice, while metrics such as densities of tip cells and vessels and ‘vascularized fraction’ are sensitive to domain choice. Given the widespread adoption and attractive simplicity of planar tissue domains, both in silico and in vitro, the differences identified in the present study should prove useful in relating the results of previous and future theoretical studies of neovascularization to in vivo observations in the cornea

Physical activity in relation to knee cartilage T2 progression measured with 3 T MRI over a period of 4 years: data from the Osteoarthritis Initiative

ObjectiveThe purpose of this study was to analyze the longitudinal association between physical activity levels and early degenerative cartilage changes in the knee, measured using T2 relaxation times over a period of 4 years in individuals without clinical or radiographic evidence of OA.DesignCartilage T2 was measured at baseline and after 2 and 4 years in 205 subjects aged 45-60 years from the Osteoarthritis Initiative (OAI) incidence and normal cohorts with no knee pain (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of zero), and a Kellgren Lawrence (KL) score of <2 at baseline. Physical activity was scored using the Physical Activity Scale for the Elderly (PASE) questionnaire, which was obtained yearly over 4 years. The relationship between physical activity and T2 was studied using a mixed model linear regression, including random effects, and adjusted for age, sex, and body mass index (BMI).ResultsT2 values for all PASE tertiles progressed over the 4-year period. T2 progression was increased in the highest tertile of physical activity compared to the mid-tertile at the medial tibia (MT) (P = 0.041), patella (Pat) (P = 0.019), and average T2 of all knee compartments combined (P = 0.033). Subjects with the lowest 15% PASE scores showed significantly higher T2 progression compared to the mid-level physical activity group at the lateral femur (LF) (P = 0.025), lateral tibia (LT) (P = 0.043), medial femur (MF) (P = 0.044), tibiofemoral compartment (P = 0.017), patellofemoral compartment (P = 0.016), lateral compartments (P = 0.003), and average of all compartments (P = 0.043).ConclusionHigh and very low PASE scores were associated with greater progression of cartilage T2 measurements in asymptomatic, middle-aged individuals, suggesting accelerated cartilage matrix biochemical degeneration over time

Structure, Thermodynamics, and Folding Pathways for a Tryptophan Zipper as a Function of Local Rigidification

We investigate how the underlying potential energy landscape for a tryptophan zipper changes as indole rings, peptide bonds, termini, and trigonal planar centers are systematically grouped into local rigid bodies. The local rigid body framework results in a substantial computational speedup by effectively reducing the total number of degrees of freedom. Benchmarks are presented for the thermodynamics and folding mechanism. In general, the melting transition, as well as the precise sequence of folding events, is accurately reproduced with conservative local rigidification. However, aggressive rigidification leads to increased topological frustration and a concomitant slowing down of the global kinetics. Our results suggest that an optimal choice of local rigidification, and perhaps a hierarchical approach, could be very useful for investigating complex pathways in biomolecules.J.A.J. acknowledges financial support from the Gates Cambridge Trust